Translational Neuroimaging in Unipolar Depression: Towards Personalized Treatment

单相抑郁症的转化神经影像学：走向个性化治疗

• 批准号: 7884525
• 负责人: GREG J SIEGLE
• 金额: $ 11.85万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7884525
• 关键词: Accounting; Address; Adult; Affect; Age; Algorithms; Amygdaloid structure; Antidepressive Agents; Anxiety; Area; Attention; Award; Basic Science; Behavior Therapy; Behavioral; Biological Factors; Brain; Brain region; Clinic; Clinical; Clinical Trials; Clinical assessments; Cognitive; Cognitive Therapy; Collaborations; Computer Simulation; Data; Data Collection; Depressed mood; Development; Disease; Elderly; Emotional; Emotions; Environment; Evaluation; Exercise; Flowers; Functional Imaging; Functional Magnetic Resonance Imaging; Funding; Heterogeneity; Independent Scientist Award; Individual; Individual Differences; Institutes; Intervention; Investigation; Lateral; Lead; Left; Longevity; Mental Depression; Mentored Research Scientist Development Award; Methods; Mydriasis; Neurophysiology - biologic function; Neurosciences; Outcome; Patients; Peripheral; Pharmaceutical Preparations; Physiological; Population; Prefrontal Cortex; Process; Proxy; Psychologist; Psychophysiology; Recovery; Research; Research Personnel; Role; Sampling; Science; Seeds; Silk; Stimulus; Supervision; System; Testing; Time; Training; Translating; Translational Research; Translations; Unipolar Depression; Vision; Work; Youth; base; cognitive control; conventional therapy; depressive symptoms; design; emotion regulation; emotional stimulus; executive function; geriatric depression; high standard; improved; information processing; insight; middle age; mild neurocognitive impairment; neuroimaging; neuromechanism; novel; preconditioning; prevent; programs; relating to nervous system; response; service intervention; therapy development; treatment planning; treatment response; vigilance

DESCRIPTION (provided by applicant): The best first-line treatments work for approximately 40-60% of unipolar depressed adults, potentially due to the disorder's complexity and heterogeneity. Basic research on the neural mechanisms of depression, assessed using functional neuroimaging has blossomed in the past decade. The proposed research will combine neuroimaging, behavioral/psychophysiological assessment, and clinical trials to allow rigorous translation of this basic science to the clinic. This work will help to direct patients specifically to treatments that will address their particular mechanisms and could lead to the development of novel neuroscience-based interventions. Such translational research has been done almost exclusively in mid-life adults. Yet, attention has increasingly focused on the extent to which interventions that address relevant brain mechanisms in mid-life individuals (e.g., Cognitive Behavioral Therapy, SSRI's) might be useful with vulnerable or depressed youth and elderly depressed individuals. Increasing research suggests that the same mechanisms which are disrupted in mid-life depression, and which are targeted in therapy, such as increased limbic response to emotional stimuli, are present in anxious youth (Easter et al 2005) who are vulnerable to depression, and may further predict treatment response in these individuals (McClure et al in press-a). Similarly, hallmarks of dysregulated emotion in depression which predict treatment response in mid-life individuals such as decreased prefrontal function are present in a high proportion of elderly depressed adults (e.g., Alexopoulos et al., 2000) and may thus be as, or more important to address in planning treatments in that population. Thus, a life-span developmental perspective will be a key generalization of ongoing translational neuroimaging research. Dr. Siegle is uniquely poised to make significant advances in this type of translational research. Following his training as a clinical psychologist and cognitive neuroscientist, his K01 award yielded computational modeling and neuroimaging data that lead to specific predictions about recovery from depression. Western Psychiatric Institute and Clinic provides a highly collaborative clinical trials environment, allowing him to test these hypotheses. His R01 has begun this work, adding assessments to existing clinical trials and collaborating with established clinical trials researchers. To continue his clinical translations to the high standards of his basic research, Dr. Siegle proposes to receive additional training and supervision in the design, execution, and evaluation of clinical trials for conventional and novel interventions. In addition, Dr. Siegle's research has focused on mid-life depressed individuals, but is increasingly being applied to understanding clinical outcomes in youth and late-life individuals. Obtaining training in potential issues associated with generalizing to the entire lifespan will be important for allowing him to advise such translations.

描述（由申请人提供）：最好的一线治疗对大约 40-60% 的单相抑郁成人有效，可能是由于该疾病的复杂性和异质性。使用功能神经影像学评估的抑郁症神经机制的基础研究在过去十年中蓬勃发展。拟议的研究将结合神经影像学、行为/心理生理学评估和临床试验，以便将这一基础科学严格转化为临床。这项工作将有助于指导患者进行针对性的治疗，以解决其特定的机制，并可能导致基于神经科学的新型干预措施的发展。这种转化研究几乎都是在中年成年人身上进行的。然而，人们的注意力越来越集中在解决中年个体相关大脑机制的干预措施（例如认知行为疗法，SSRI）对脆弱或抑郁的青少年和老年抑郁个体可能有用的程度。越来越多的研究表明，在中年抑郁症中被破坏的相同机制，以及治疗中的目标，例如边缘系统对情绪刺激的反应增加，也存在于易患抑郁症的焦虑青少年中（Easter et al 2005），并且可以进一步预测这些个体的治疗反应（McClure et al in press-a）。同样，抑郁症情绪失调的标志（预测中年个体的治疗反应，例如前额叶功能下降）存在于高比例的老年抑郁症成人中（例如，Alexopoulos 等人，2000），因此在规划该人群的治疗时解决或更重要。因此，生命周期发展的视角将是正在进行的转化神经影像研究的关键概括。西格尔博士具有独特的优势，有望在此类转化研究中取得重大进展。在接受临床心理学家和认知神经科学家培训后，他的 K01 奖产生了计算模型和神经影像数据，从而对抑郁症的恢复做出了具体预测。西方精神病学研究所和诊所提供了高度协作的临床试验环境，使他能够检验这些假设。他的 R01 已经开始这项工作，为现有的临床试验添加评估，并与成熟的临床试验研究人员合作。为了继续将他的临床转化达到高标准的基础研究，西格尔博士建议在传统和新型干预措施的临床试验的设计、执行和评估方面接受额外的培训和监督。此外，西格尔博士的研究重点是中年抑郁症患者，但越来越多地应用于了解青年和晚年患者的临床结果。获得与推广到整个生命周期相关的潜在问题的培训对于让他为此类翻译提供建议非常重要。